THE ABILITY OF PEPTIDES TO INDUCE CYTOTOXIC T-CELLS IN-VITRO DOES NOTSTRONGLY CORRELATE WITH THEIR AFFINITY FOR THE H-2L(D) MOLECULE - IMPLICATIONS FOR VACCINE DESIGN AND IMMUNOTHERAPY

The hypothesis that the ability of a peptide to bind to a class I mole cule correlates with its immunogenicity is controversial. In this pape r we have measured the affinity constants of nine synthetic peptides, which have been previously identified as binding to H-2L(d) molecules, and have determined their immunogenicity in an in vitro cytotoxic T l ymphocyte (CTL) induction assay. We find that six peptides bind with h igh affinity (K-a>10(7)/M); of these, four are of viral origin but onl y two elicit potent CTLs, one is a self peptide which is not immunogen ic, while the sixth is of bacterial origin and also does not generate effective CTLs. Two peptides bind with intermediate affinity (K-a>10(6 )/M); one of these elicits a moderate CTL response, while the other, a tumor-derived epitope, is highly immunogenic. Intriguingly, the pepti de with lowest affinity (p2Ca) is exceedingly effective at eliciting C TLs. The efficacy of peptides with modest affinity for their restricti on elements appears to correlate well with the CTL precursor frequency . We have also examined intrinsic parameters of some of the peptides s uch as solubility and stability. Taken together, our results underscor e the relevance of factors other than affinity which affect immunogeni city and which may be critical in the design of peptide-based vaccines as well as tumor immunotherapy approaches. (C) 1997 Elsevier Science Ltd.